Dataset Information

C-Myc suppresses miR-451?YWTAZ/AKT axis via recruiting HDAC3 in acute myeloid leukemia.

ABSTRACT: Aberrant activation of c-Myc plays an important oncogenic role via regulating a series of coding and non-coding genes in acute myeloid leukemia (AML). Histone deacetylases (HDACs) can remove acetyl group from histone and regulate gene expression via changing chromatin structure. Here, we found miR-451 is abnormally down-regulated in AML patient samples; c-Myc recruits HDAC3 to form a transcriptional suppressor complex, co-localizes on the miR-451 promoter, epigenetically inhibits its transcription and finally induces its downregulation in AML. Furthermore, our in vitro and in vivo results suggest that miR-451 functions as a tumor suppressor via promoting apoptosis and suppressing malignant cell proliferation. The mechanistic study demonstrated that miR-451 directly targets YWHAZ mRNA and suppresses YWHAZ/AKT signaling in AML. Knockdown of c-Myc results in restoration of miR-451 and inhibition of YWHAZ/AKT signaling. In AML patients, low level of miR-451 is negatively correlated with high levels of c-Myc and YWHAZ, while c-Myc level is positively related to YWHAZ expression. These results suggested that c-Myc?miR-451?YWHAZ/AKT cascade might play a crucial role during leukemogenesis, and reintroduction of miR-451 could be as a potential strategy for AML therapy.

SUBMITTER: Su R

PROVIDER: S-EPMC5363596 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

c-Myc suppresses miR-451⊣YWTAZ/AKT axis via recruiting HDAC3 in acute myeloid leukemia.

Su Rui R Gong Jia-Nan JN Chen Ming-Tai MT Song Li L Shen Chao C Zhang Xin-Hua XH Yin Xiao-Lin XL Ning Hong-Mei HM Liu Bing B Wang Fang F Ma Yan-Ni YN Zhao Hua-Lu HL Yu Jia J Zhang Jun-Wu JW

Oncotarget 20161101 47

Aberrant activation of c-Myc plays an important oncogenic role via regulating a series of coding and non-coding genes in acute myeloid leukemia (AML). Histone deacetylases (HDACs) can remove acetyl group from histone and regulate gene expression via changing chromatin structure. Here, we found miR-451 is abnormally down-regulated in AML patient samples; c-Myc recruits HDAC3 to form a transcriptional suppressor complex, co-localizes on the miR-451 promoter, epigenetically inhibits its transcripti ...[more]

PMID: 27764807

Similar Datasets

Project description:BackgroundTreatment of metastatic castration-resistant prostate cancer (mCRPC) with docetaxel often fails due to the emergence of chemoresistance. Thus, restoring chemosensitivity to docetaxel-based therapies remains a challenge in mCRPC treatment.MethodsmicroRNA (miR)-451 expression was measured in docetaxel-treated prostate cancer cells and tumor tissues by quantitative reverse-transcription polymerase chain reaction . Cell-counting kit 8 assay was performed to determine docetaxel chemoresistance. Neural-precursor-cell-expressed developmentally downregulated protein 9 (NEDD9) was identified as a novel target of miR-451 by dual-luciferase reporter system. Chromatin immunoprecipitation and co-immunoprecipitation assay were performed to confirm that histone deacetylase 3 (HDAC3)/Sp1 (a highly evolutionarily conserved transcription factor) interacted with the Sp1 binding sites in miR-451 promoter.ResultsmiR-451 was found to be silenced in docetaxel-treated prostate cancer cells and mCRPC tissues. Low miR-451 expression was closely associated with a high Gleason score, high Eastern Cooperative Oncology Group performance status score, visceral metastasis and poor prognosis. Low expression of miR-451 was significantly correlated with short progression-free survival (PFS) and overall survival (OS) according to Kaplan-Meier analysis, and miR-451 was determined to be an independent poor prognostic factor for PFS and OS in mCRPC patients by univariate and multivariate Cox regression analyses. NEDD9 was identified as a new and functional target of miR-451. Restoration of NEDD9 partially reversed the effects of miR-451 on enhancing chemosensitivity of prostate cancer cells. HDAC3 was confirmed to be involved in silencing of miR-451 expression in prostate cancer cells.ConclusionsThe current data revealed a new HDAC3/Sp1/miR-451/NEDD9 signaling axis that regulates the chemosensitivity of prostate cancer cells and represents a novel therapeutic target for chemosensitizing mCRPC.

Dataset Information

C-Myc suppresses miR-451?YWTAZ/AKT axis via recruiting HDAC3 in acute myeloid leukemia.

Publications

c-Myc suppresses miR-451⊣YWTAZ/AKT axis via recruiting HDAC3 in acute myeloid leukemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets